Sepsis
Conditions
Keywords
Sepsis, Racecadotril, organ dysfunction
Brief summary
In this single-center, single-blind, randomized, placebo-controlled pilot trial. The effect of Racecadotril on the improvement of organ function will be investigated in patients with sepsis. Researchers will screen patients admitted to the Department of Critical Care Medicine at Zhujiang Hospital to identify patients with sepsis based on including and excluding criteria and obtain informed consent and randomize them into groups. On the basis of standardized treatment for sepsis, the Racecadotril group will be given Racecadotril Granules at a dose of 1.5mg/kg reconstituted in 20ml of water for nasal feeding tube, three times daily; the Control group will be given an 20ml of water for nasal feeding tube,three times daily. The changes in SOFA-2 score and other clinically meaningful outcomes in 4 days will be collected. For subjects whose treatment lasts less than 4 days, the changes on the date of ICU discharge will be used.
Detailed description
Investigational drug: Racecadotril Granules Study title: Racecadotril for Organ Injury in Sepsis Patients: A Single-Center, Single-Blind, Randomized, Placebo-Controlled Pilot Trial Principal Investigator: Zhanguo Liu, professor, Department of Critical Care Medicine, Zhujiang Hospital, Southern Medical University Study subjects: Patients diagnosed with sepsis according to the SOFA-2 scoring criteria published by JAMA in 2025 (PMID: 41159833). Study objectives: The objective of the study is to determine whether Racecadotril, compared to placebo, improves organ dysfunction scores (SOFA -2 scores) in septic patients. Study design: A single-center, single-blind, randomized, placebo-controlled pilot trial. Method: On the basis of standardized treatment for sepsis, the Racecadotril group will be given Racecadotril Granules at a dose of 1.5mg/kg reconstituted in 20ml of water for nasal feeding tube, three times daily; the Control group will be given an equal volume of water for nasal feeding tube,three times daily, intervention for 4 days or until ICU discharge(whatever come first). Course: 4 days Sample size: 44 The number of study center: 1 Study center: 1\. Department of Critical Care Medicine of Zhujiang Hospital,Southern Medical University,Guangzhou, China Primary endpoint: 96-hour Sequential Organ Failure Assessment-2 (SOFA-2) score Secondary endpoints: 1. The blood routine examination: White blood cell count, neutrophil count, neutrophil ratio, lymphocyte count, lymphocyte ratio, platelet count at 96 h after first treatment administration. 2. The state of liver function: the serum level of transaminase (AST and ATL) and total bilirubin at 96 h after first treatment administration. 3. The state of kidney function: the serum level of Creatinine (Cr)#blood urea nitrogen (BUN)# and daily urine output at 96 h after first treatment administration. 4. The state of circulation system: Blood pressure, the duration and dosage of vasopressor drugs, and the serum level of lactate at 96 h after first treatment administration. 5. The state of lung function: oxygenation index(PaO2/FiO2), partial pressure of oxygen, partial pressure of carbon dioxide at 96 h after first treatment administration. 6. The state of inflammatory response: the serum level of interleukin-6(L-6) and C-reactive protein (CRP) at 96 h after first treatment administration. 7. The state of infection: the serum level of procalcitonin (PCT) at 96 h after first treatment administration. 8. The organ function support status: mechanical ventilation, RT treatment status, ECMO support status at 96 h after first treatment administration. 9. The critical score: APAPCHE II score at 96 h after first treatment administration. Safety endpoints: 1. Safety evaluation indicators: Possible adverse reactions of Racecadotril may include (drowsiness, rash, constipation, nausea, abdominal pain), survival status on the 28th day. 2. Feasibility evaluation indicators: Record the specific number of days and times that patients used Racecadotril; ICU hospitalization days. For subjects whose treatment lasts less than 4 days, the changes on the date of ICU discharge will be used.
Interventions
DRUGRacecadotril
On the basis of standardized treatment for sepsis, the Racecadotril group will be given Racecadotril Granules at a dose of 1.5mg/kg reconstituted in 20ml of water for nasal feeding tube, three times daily for 4 consecutive days
DRUGWater (Placebo)
On the basis of standardized treatment for sepsis, 20ml of water for nasal feeding tube, three times daily for 4 consecutive days
Sponsors
Zhujiang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. diagnosed with sepsis according to the SOFA-2 scoring criteria published in 2025 JAMA(PMID:41159833); 2. SOFA-2 score: 6 - 14 points; 3. subjects who voluntarily participated in this study and signed an informed consent form. 4. age 18 - 80 years.
Exclusion criteria
1. Patients with a known allergy to the study product. 2. Patients unable to receive enteral nutrition via a gastrointestinal tube. 3. Patients with hepatic insufficiency: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both greater than 3 times the upper limit of normal. 4. Patients with renal dysfunction: Acute kidney injury (AKI) ; chronic kidney disease (CKD) stage 3 or higher. 5. Patients receiving medications at the start of the study that may significantly interfere with the pharmacodynamics and metabolism of Racecadotril, or increase its toxicity(Such as Erythromycin, Ketoconazole, Rifampicin). 6. Patients with fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency. 7. Pregnant or breastfeeding women. 8. Patients with limited nursing care (patients for whom active treatment has been withdrawn).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 96-hour Sequential Organ Failure Assessment-2 (SOFA-2) score | Day0,Day1,Day2,Day3,Day4 | The SOFA-2 score is the Sequential Organ Failure Score-2, which is used to assess a patient's prognosis by determining the degree of impairment of major organ function. The score is divided into 6 sections: respiratory, coagulation, hepatic, cardiovascular, central nervous system, and renal, and ranges from 0 to 4, resulting in a total score ranging from a minimum of 0 to a maximum of 24 points, with higher SOFA-2 scores associated with a higher incidence of poor prognosis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| blood routine examination(6) - platelet count | Day0,Day1,Day2,Day3,Day4 | platelet count |
| liver function(1) - ALT | Day0,Day1,Day2,Day3,Day4 | the serum level of Alanine transaminase(ALT) |
| liver function(2) - AST | Day0,Day1,Day2,Day3,Day4 | the serum level of Aspartate transaminase (AST) |
| liver function(3) - TBil | Day0,Day1,Day2,Day3,Day4 | the serum level of total bilirubin(TBil) |
| kidney function(1) - Cr | Day0,Day1,Day2,Day3,Day4 | serum level of Creatinine (Cr) |
| kidney function(2) - BUN | Day0,Day1,Day2,Day3,Day4 | serum level of blood urea nitrogen(BUN) |
| kidney function(3) - daily urine output | Day0,Day1,Day2,Day3,Day4 | daily urine output in milliliters from 0:00 - 24:00 |
| circular evaluation index(1) - BP | Day0,Day1,Day2,Day3,Day4 | blood pressure |
| blood routine examination(1) - white blood cell count | Day0,Day1,Day2,Day3,Day4 | white blood cell count |
| blood routine examination(2) - neutrophil count | Day0,Day1,Day2,Day3,Day4 | neutrophil count |
| blood routine examination(3) - neutral cytoplasmic ratio | Day0,Day1,Day2,Day3,Day4 | neutral cytoplasmic ratio |
| blood routine examination(4) - lymphocyte count | Day0,Day1,Day2,Day3,Day4 | lymphocyte count |
| circular evaluation index(2) - the duration and dosage of vasoactive drugs | Day0,Day1,Day2,Day3,Day4 | the duration and dosage of vasoactive drugs. The duration from the vasoactive drugs administration to the successful cessation in hours( The successful cessation is defined as the attainment of a clinician-prescribed mean arterial pressure target for more than 24-hours without the use of vasoactive drugs. This outcome measure is intended only for patients receiving vasoactive drugs) |
| circular evaluation index(3) - Lac | Day1,Day2,Day3,Day4 | the serum level of lactic acid |
| lung function(1) - PaO2/FiO2 | Day0,Day1,Day2,Day3,Day4 | oxygenation index(PaO2/FiO2),the patients treated with extracorporeal membrane oxygenation will not collect this indicator |
| lung function(2) - PaO2 | Day0,Day1,Day2,Day3,Day4 | oxygen partial pressure(PaO2) |
| lung function(3) - PaCO2 | Day0,Day1,Day2,Day3,Day4 | partial pressure of carbon dioxide(PaCO2) |
| inflammatory response(1) - CRP | Day0,Day1,Day2,Day3,Day4 | the serum level of C-reactive protein(CRP) |
| inflammatory response(2) - IL-6 | Day0,Day1,Day2,Day3,Day4 | the serum level of interleukin-6(IL-6) |
| Indicators of infection | Day0,Day1,Day2,Day3,Day4 | the serum level of procalcitonin(PCT) |
| organ function support status(1) - the duration of use of MV | Day0,Day1,Day2,Day3,Day4 | the duration of use of mechanical ventilation (MV).The duration from the MV administration to the successful cessation in hours( The successful cessation is defined as the termination of MV for more than 48-hours. This outcome measure is intended only for patients receiving MV) |
| organ function support status(2) - The duration of CRRT | Day0,Day1,Day2,Day3,Day4 | The duration of CRRT.The duration of CRRT therapy in hours |
| organ function support status(3) - The duration of ECMO | Day0,Day1,Day2,Day3,Day4 | The duration of ECMO.The duration of ECMO therapy in hours |
| blood routine examination(5) - lymphocyte ratio | Day0,Day1,Day2,Day3,Day4 | lymphocyte ratio |
| The critical score - APAPCHE II score | Day0,Day1,Day2,Day3,Day4 | APAPCHE II score （Acute Physiology and Chronic Health Evaluation II） has a scoring range of 0 to 71 points. A higher score indicates a worse outcome, signifying a more critical patient condition and a correspondingly increased risk of mortality. It is a commonly used tool in Intensive Care Units (ICUs) for assessing the severity of a patient's illness and predicting prognosis. |
Countries
China
Contacts
CONTACTZhanguo Liu, M.D.PhD
PRINCIPAL_INVESTIGATORZhanguo Liu, M.D.PhD
Department of Critical Care Medicine of Zhujiang Hospital
Outcome results
None listed